Disruption of the p70(s6k)/p85(s6k) gene reveals a small mouse phenotype and a new functional S6 kinase

Shima H, Pende M, Chen Y, Fumagalli S, Thomas G, Kozma SC · 1998 · EMBO Journal · Atlas ID SHI1998

What this study shows

Mice with the S6K1 gene disrupted were viable and fertile but smaller, with the growth effect strongest during embryonic development. Unexpectedly, ribosomal protein S6 was still phosphorylated normally after mitogen stimulation in knockout liver and fibroblasts, and in knockout fibroblasts S6 phosphorylation and the rise in 5'TOP mRNA translation were as sensitive to rapamycin as in wild-type cells. A database search identified a second S6 kinase, S6K2, which had mitogen-dependent and rapamycin-sensitive S6 kinase activity and was up-regulated in all tissues of the knockout mice examined, most of all in thymus. S6K2 can therefore partly compensate for loss of S6K1. Boundary: Mouse knockout and mouse cells. Body size and S6 signalling only; the 5'TOP result means S6K1 alone is not required in these cells, not that S6 kinases are irrelevant. Drafted from the abstract only.

Abstract

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Recent studies have shown that the p70(s6k)/p85(s6k) signaling pathway plays a critical role in cell growth by modulating the translation of a family of mRNAs termed 5'TOPs, which encode components of the protein synthetic apparatus. Here we demonstrate that homozygous disruption of the p70(s6k)/p85(s6k) gene does not affect viability or fertility of mice, but that it has a significant effect on animal growth, especially during embryogenesis. Surprisingly, S6 phosphorylation in liver or in fibroblasts from p70(s6k)/p85(s6k)-deficient mice proceeds normally in response to mitogen stimulation.

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At a glance

Evidence type	A Animal model Marked A because it is an animal intervention or observation study measuring an organismal outcome (model: p70/p85 S6K1 knockout mice; embryonic fibroblasts and liver from knockout mice; S6K2 cloning and kinase assays); the code names the system studied -- animal work can be rigorous and still not be human data.
Study type	4 - Animal Study
Model system	p70/p85 S6K1 knockout mice; embryonic fibroblasts and liver from knockout mice; S6K2 cloning and kinase assays
Journal	EMBO Journal
Year	1998
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1093/emboj/17.22.6649 · PMID 9822608 · Free full text (PMC1171010)

Extracted findings

These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.

Intervention	Germline S6K1 (p70/p85 S6K) knockout; rapamycin in knockout fibroblasts
Target	Body size; S6 phosphorylation; 5'TOP mRNA translation; S6K2 expression
Model	Mouse
Effect	Loss of S6K1 reduces body size, especially embryonic growth, while S6 phosphorylation and rapamycin-sensitive 5'TOP translation persist via S6K2

In the Atlas

Cite this paper

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Shima, H., Pende, M., Chen, Y., Fumagalli, S., Thomas, G., & Kozma, S. C. (1998). Disruption of the p70(s6k)/p85(s6k) gene reveals a small mouse phenotype and a new functional S6 kinase. EMBO Journal. https://doi.org/10.1093/emboj/17.22.6649

@article{SHI1998,
  author       = {Shima, H. and Pende, M. and Chen, Y. and Fumagalli, S. and Thomas, G. and Kozma, S. C.},
  title        = {{Disruption of the p70(s6k)/p85(s6k) gene reveals a small mouse phenotype and a new functional S6 kinase}},
  journal      = {EMBO Journal},
  year         = {1998},
  doi          = {10.1093/emboj/17.22.6649},
  note         = {PMID: 9822608},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper.

Barton, O. (2026). Oliver's mTOR Atlas (record SHI1998) [Data set]. https://mtor-atlas.org/study/SHI1998/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_SHI1998,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record SHI1998},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/SHI1998/},
  doi          = {10.5281/zenodo.22059963}
}

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